Background/Purpose:
IL-6 is a pivotal cytokine in PMR pathogenesis, yet the efficacy of IL-6 blockade
with tocilizumab (TCZ) for treatment of PMR is unknown. The aim of this study
was to assess the efficacy and safety of TCZ for treatment of newly diagnosed
PMR.

Methods: In a
single-center open-label study, subjects with newly diagnosed PMR (Healey
criteria) and prior treatment with <1 month (mo) of corticosteroids (CS)
were treated with TCZ 8mg/kg IV monthly for 12 mos plus a rapid CS taper.
Subjects were followed for 15 mos. Those with concurrent GCA or those treated
with >30mg prednisone were excluded. Primary endpoint was the proportion of
subjects in relapse-free remission off CS at 6 mos. A cohort of consecutively
evaluated patients with newly diagnosed PMR who declined participation in the
trial or failed to meet inclusion criteria served as a control group. These
patients were treated contemporaneously by a single rheumatologist with
expertise in PMR and received CS alone, tapered at the treating physician’s
discretion.

Results:

Primary
endpoint: Ten subjects were enrolled. All 10 also met ACR/EULAR 2012
Provisional Classification Criteria for PMR. One subject withdrew after 2 mos
due to a mild infusion reaction, leaving 9 subjects in whom primary endpoint
was assessed. 9/9 subjects achieved the primary endpoint of relapse-free
remission off CS at 6 mos. Of the 7 subjects who have reached 12 mos in the
study to date, all remained in remission without relapse, as did all 4 of those
who have thus far completed their 15 mos of follow-up. No flares in subjects
treated with TCZ were observed throughout the study.

Ten controls were identified who had been seen consecutively
with newly diagnosed PMR. Controls did not differ from study subjects with
regard to age, gender, acute phase reactants, or mean baseline CS dose [Table
1]. No controls were in remission off of CS at 6 mos. At 12 mos, a 60% relapse
rate was observed in controls.

Steroid-sparing
effects: 8/9 TCZ-treated subjects were able to discontinue CS
following the third TCZ dose; one subject tapered off CS following the fourth
TCZ dose. No subjects receiving TCZ required resumption of CS once they had
been tapered off. Cumulative prednisone dose in subjects was 1085±301mg compared to 2562±1356mg in controls (p-value 0.01). Total
duration of steroid exposure was significantly less in subjects (3.9±0.9 mos) compared to the controls (14.1±6.0 mos), p-value 0.002 [Table 1].

Safety:
22 adverse events were observed in subjects on TCZ (1 infusion reaction, 5
URIs, 5 episodes of mild neutropenia); only one SAE observed (subject
hospitalized after motor vehicle accident).

Conclusion: In this
study, TCZ was an effective,
safe and well-tolerated treatment for newly diagnosed PMR with a robust
steroid-sparing effect compared to contemporaneously-treated controls. Subjects
treated with TCZ received on average <4 mos of CS and enjoyed relapse-free
remission out to 15 mos.